Case Record 7

Normal Tension Glaucoma

January 2012

Dr Peter Frampton

DOptom MSc FCOptom

BAppSc(Optom)(AUS) DipTp(AS)

DipTp(SP) DipTp(IP)

Introduction and Definition

The existence of ‘Normal Tension Glaucoma’ (NTG) was not firmly

established until the mid twentieth century (Werner 1996). The working

definition adopted by Werner is :

‘…..a condition in which cupping of the optic nerve head, loss of the

retinal nerve fibre layer and visual field defects similar to those seen in

other forms of chronic glaucoma are seen, and in which an intraocular

pressure level outside the statistically normal range without treatment has

not been documented, nor is any other cause for these changes apparent’.

The final point within the definition would suggest that the diagnosis of

‘Normal Tension Glaucoma’ is necessarily one of exclusion. Baig,

Akram, Ishaq and Raja (2002) and Choudhari, Neog, Fudnawala and

George (2011) report cases of conditions mimicking glaucoma being

misdiagnosis as NTG. Karmel (2006) notes that NTG usually occurs over

the age of 60; younger patients should arouse suspicion of alternate

pathologies. Werner (1996) also remarks that the differential diagnosis

must consider the possibility of undetected high-tension glaucoma.

The lack of consensus regarding the risk factors for glaucoma

progression, coupled with the known risks of aggressive treatments, made

management decisions difficult (Anderson 2003). Prior to the

‘Collaborative Normal-Tension Glaucoma Study’ strong opinion

advocated that treatment would not be of help to patients with NTG

(Karmel 2006).

The Collaborative Normal-Tension Glaucoma Study Group (1998a)

demonstrated categorically that a 30% reduction in IOP slowed the rate of

VF progression. However the same group (1998b) report that progression

still occurred in a proportion of patients regardless of this level of IOP

control, suggesting either the need for greater IOP reduction for these

patients or the presence of other pathogenic factors.

This would seem likely. Reduced outflow facility is implicated in most

glaucomas (Toris and Camras 2007) but is near normal in NTG (Werner

1996). Systemic hypotension, particularly nocturnal dips, general

vascular disease and vasospastic phenomena are all associated with NTG.

The higher instance of disc haemorrhages with NTG (European

Glaucoma Society 2003, Werner 1996) also suggests local vascular

insufficiencies.

December 2006

Diagnosis of NTG

Salient information taken from electronic records

DATE: 21/12/06

Mrs Age 45

Address

Presenting Symptoms

First Eye Exam. Reading becoming difficult. Distance good unaided. No

diplopia. No HAs.

POH

None : first examination. No previous ocular surgery or treatments.

FOH

None.

General Health and Medications

Non-smoker. No Allergies, No Hayfever

Migraines – many years. Left sided. 2 to 3 times per month. No ‘Red

Flags’ Debilitating. Acute meds only (OTC) Ibuprofen. No prophylaxis,

no Triptans.

Long term Hyperlipidemia - Simvastatin 20mg nightly

Otherwise general health good, no heart, breathing or vascular problems.

BP reported as good.

No previous history of general or ocular medication use or surgery.

Refraction

R Plano /-0.50x140 (6/4.8-) Add +1.00 N5

L +0.25/-0.75x40 (6/4.8-) Add +1.00 N5

Tensions (GAT) R 12 L 10 Glaucoma Fast Treshold

Pupils E&A D,C& N attached

Slit Lamp

VH 3 open, Corneas clear. No Pigmentation, Iris normal.

Dilated Fundsocopy (1% Tropicamide)

Right Disc – VCD 0.8 – Possible superior bayoneting.

Left Disc - VCD 0.7 Inferior Rim notch with baring of inferior

circumlinear vessel. Possible superior bayonetting

Advice and CMP

Glaucoma discussed and Glaucoma test leaflet given.

GDx advised but declined

Presbyopia explained.

Fields and GAT repeated 22/12/06. Referred to ophthalmology.

Pattern Defect 4.02*

Cluster analysis : Suspect Superior Defect

Overall Defect : 0.74

Left GFT 21/12/06 Pattern Defect 9.75***

Cluster analysis Superior Depression

Overall Defect 2.69

Left GFT 22/12/06

Pattern Defect : 5.72**

Cluster analysis : Superior Defect

Overall Defect : 3.47

Normal-tension glaucoma requires a high index of suspicion (Werner

1996). In this case the patient presented coincidentally as an early

presbyope, with no previous ocular history. No family history of

glaucoma was reported; routine measurement of IOP was R 12 and L

11mmHg. A history of migraine was described but did not raise the level

of suspicion.

Volk examination of the discs triggered more in-depth considerations of

optic neuropathy. The left disc in particular showed thinning of the

inferior rim and barring of the inferior circumlinear vessel (European

Glaucoma Society 2003, Airaksinen, Tuulonen and Werner 1996).

Glaucoma Fast Threshold testing was conducted at the initial

examination. Reliability indices were good. Pattern defects were flagged

as very significant for the left (9.74***). Cluster Analysis was also

significant as classified a Superior Depression.

Statistical probability assessments by StatPac programs report the

probabilities that a particular measurement is abnormal, not that it is

abnormal. The results should lend support for clinical expectations; in

this case the pattern of arcuate loss and the statistical indices reflect the

observed thinning of the inferior neural rim.

The European Glaucoma Society (2003) stipulate field loss should be

confirmed on two consecutive tests; the left field was repeated and an

arcuate loss corresponding to the disc appearance was confirmed.

The huge variation in the field results for the left eye, taken a single day

apart, highlights the difficulties in interpreting single plots. Gillespie et al

(2003) list a plethora of variables affecting field repeatability. At the

point of diagnosis variability is of less concern as long as the overall

results support and confirm other clinical findings. Intra-observer

variability is a far more significant confounder when striving to monitor

field progression.

The possibility that the disc and field results were the result of an

alternative form of glaucoma were considered and discounted.

Angle depth was estimated as Grade III for each eye (van-Herricks); only

angles less than III have been found to be closable (Palmberg 1996).

Large circadian variations in IOP were also discounted as a cause of the

glaucomatous presentation. Mean ranges of IOP variation reported by

Zeimer (1996) are less than 5mmHg at a mean pressure of 14.1mmHg,

making it unlikely that circadian variability could result in undetected

high pressure.

The practice did not possess a pachymeter in 2006 so central corneal

thickness was not recorded. However, Brandt and co-workers (2001),

listing a number of published figures, suggest the highest correction

factor for central corneal thickness of 5mmHg per 70m, (Brandt et al

2001). Ehlers and Hansen (1974) reported that the original calibration of

the Goldmann Tonometer assumed a CCT of 500µm, while Brandt

(2004) indicated that the GAT reading most accurately reflects true IOP

when CCT is 520µm. It would therefore be unlikely that a thin CCT

could account for this level of IOP as artefact.

A routine referral via the patient’s GP was made.

Ophthalmology and Optometric Review

2007 till 2011

The Royal College of Ophthalmologists (2004) state that it is important to

confirm that the pattern of field loss and optic nerve appearance equate to

the diagnosis of glaucoma, as a differential diagnosis may include space

occupying intracranial lesions. Freudenthal (2010) goes further and

recommends the consideration of a wide range of blood, immunological

and mitochondrial checks. Many of the pathologies considered for

differential diagnosis in this paper however do exhibit classically

different presenting symptoms and signs.

This patient’s age did lead to a high index of suspicion as NTG usually

occurs over the age of 60 and younger patients should arouse suspicion of

alternate pathologies (Karmel 2006). In this case the MRI scan was

conducted in 2006 to discount co-existing pathologies. No abnormalities

were detected and this patient is being monitored as non-progressive

Normal Tension Glaucoma at this stage. Careful monitoring is essential,

especially in view of her age.

RIGHT DISC

21/12/06 12/12/07

31/3/10 19/4/11

LEFT DISC

21/12/06 12/12/07

31/3/10 19/4/11

No change has been detected in either the photographic appearance of the

discs or the visual fields recorded through the HES.

The European Glaucoma Society (2003) defines the goal of treatment for

glaucoma as : ‘preservation of visual function adequate to the individual

needs with minimal or no side effects, for the expected lifetime of the

patient, without any disruption to his/her normal activities, at a

sustainable cost’.

Anderson (2003) reports that VF progression in NTG is variable, with a

proportion of patients potentially never needing treatment. Management

strategy may well depend on the clinician’s estimate of progression,

which can only be established by monitoring the untreated condition

carefully (Anderson 2003, CNTG 1998a).

RIGHT GFT

21/12/06 PD 4.02*, OD 0.74, 12/12/07. PD 2.86*, OD 3.53

Cluster Analysis : Suspect Superior Defect Cluster Analysis : No local Defects

31/3/10 PD 2.81*, OD 2.09 19/4/11. PD 2.37, OD 2.28

Cluster Analysis : No local Defects Cluster Analysis : No local Defects

LEFT GFT

21/12/06 PD 9.74***, OD 2.69 12/12/07. PD 8.01**, OD 2.56

Cluster Analysis : Superior Depression Cluster Analysis : Superior Depression

31/3/10 PD 6.77**, OD 3.50 19/4/11. PD 9.22***, OD 1.95

Cluster Analysis : Superior Defect Cluster Analysis : Superior Depression

While our digital photographs confirm the stable appearance, the primary

measure of change and the most likely parameter to initiate a change in

treatment strategy is visual field progression (European Glaucoma

Society 2003). The fields from our practice cannot be interpreted as

demonstrating or not demonstrating progression. In the four plots

presented the Pattern Defect ranged from 9.75*** to 8.02***, back to

6.77** and finally 9.22***. The original repeat field in 2006 had a PD of

only 5.72**. Apart from 2010 when Cluster Analysis was recorded as

‘Superior Defect’ this probability index remained as ‘Superior

Depression’.

Fields are notoriously variable (Gillespie et al 2003). Interpretation of

progression is dependent on the criteria chosen. Wilson (2002), Katz et al

(1999) and the European Glaucoma Society (2003) document a number

of methodologies to assess VF progression, demonstrating varying

progression rates. Upwards of six fields and five years of data has been

reported necessary to identify visual field progression (Watson 2002),

while the Advanced Glaucoma Intervention Study found that 30% of

fields classified as progressed at 2 follow ups, failed to maintain that

classification.

Regardless of prescriber status this patient required referral for

neurological imaging.

However, if the fields were to be considered for monitoring rather than

simply referral then an original baseline would need to be set.

While quantitative methods for monitoring field progression are

published (Katz, Congdon and Friedman 1999), the European Glaucoma

Society (2003) considers a more pragmatic approach. Since glaucoma

field loss is usually slow and will rarely be detected within one year, the

society suggests 2 to 3 tests to provide a baseline to be repeated twice a

year. Stricter follow-up would be considered in advanced disease or if

field defects impinged on fixation.

Few community optometrists are, as yet, independently monitoring

glaucomatous field progression. Many optometrists have evolved from

Screeners to Diagnosticians; significant new interpretive skills will be

required if this process continues toward Community Optometrists as

primary Therapists.

REFERENCES

1. Airaksinen PJ, Tuulonen A and Werner EB. (1996). Clinical Evaluation of the Optic Disc and Retinal Nerve Fibre Layer. In Ritch R., Shields M.B. and Krupin T. The Glaucomas (Second Edition) Vol I Basic Sciences. Mosley. USA.

2. Anderson DR. (1992). Automated Static Perimetry. Mosley.

USA.

3. Anderson R. (2003). Collaborative Normal Tension Glaucoma Study. Curr Opin Opthalmology 14 : 86-90.

4. Baig MA, Akram A, Ishaq M and Raja N. (2002). Normal

Tension Glaucoma errors in diagnosis. Pakistan J Ophthalmology 18 (1) : 23-25.

5. Brandt J. (2004). Corneal thickness in glaucoma screening, diagnosis and management. Current Opinion in Ophthalmology; 15: 85-89.

6. Brandt JD, Beiser JA, Kass MA, Gordon MO and the Ocular

Hypertensive Treatment Study (OHTS) Group. (2001). Central Corneal Thickness in the Ocular Hypertensive Treatment Study (OHTS). Ophthalmology 108 (10) : 1779-1788.

7. Choudhari N, Neog A, Fudnawala V and Geroge R. (2011). Cupped Disc with Normal Tension Glaucoma: The long road to avoid misdiagnosis. Indian Journal of Ophthalmology; 59(6): 491-497.

8. Collaborative Normal-Tension Glaucoma Study Group.

(1998a). Comparison of Glaucomatous Progression Between Untreated Patients With Normal-Tension Glaucoma and Patients with Therapeutically Reduced Intraocular Pressure. American Journal of Ophthalmology 126 (4) : 487-497

9. Collaborative Normal-Tension Glaucoma Study Group.

(1998b). The Effectiveness of Intraocular Pressure Reduction in the Treatment of Normal-Tension Glaucoma. American Journal of Ophthalmology 126 (4) : 498-505.

10. Ehlers N and Hansen F. (1974). Central Corneal Thickness in Low-Tension Glaucoma. ACTA Ophthalmologica; 52: 740-746.

11. European Glaucoma Society. (2003). Terminology and

Guidelines for Glaucoma Edition II. Dogma. Accessed www.eugs.org

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PA and the CIGTS Study Group. (2003). The Collaborative Initial Glaucoma Treatment Study : Baseline Visual Field and Test-Retest Variability. Investigative Ophthalmology and Visual Science 44 (6) : 2613-2620.

14. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner

JL, Miller JP, Parrish RK, Wilson MR and Gordon MO for the Ocular Hypertensive Treatment Study Group. (2002). The Ocular Hypertensive Treatment Study : A Randomized Trial Determines That Topical Ocular Hypotensive Medications Delays or Prevents the Onset of Primary Open-Angle Glaucoma. Arch Ophthal; 120 : 701-713.

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and Krupin T. The Glaucomas (Second Edition) Vol I Basic Sciences . Mosley. USA.

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Pressure. In Ritch R., Shields M.B. and Krupin T. The Glaucomas (Second Edition) Vol I Basic Sciences . Mosley. USA.